# Project 3 (Mercola)

> **NIH NIH P01** · STANFORD UNIVERSITY · 2021 · $513,960

## Abstract

SUMMARY
Project 3: iPSC-CM Screening to Discover Mechanisms and Therapeutic Targets
Heart failure (HF) is major cause of morbidity and mortality worldwide and affects 1–2% of the US
population and represents a major public health burden. Heart failure patients are particularly
sensitive to arrhythmia. Up to 50% of HF patients die from arrhythmias and sudden cardiac death,
creating a precarious health risk, yet few drugs are effective in this population. Project 3 of this PPG
addresses two major questions relevant to the clinical management of these patients: 1) Why are HF
patients particularly susceptible to drug-induced arrhythmia (Aim 1) and 2) Can we discover proteins
that can be targeted pharmaceutically to create entirely new classes of drugs to treat arrhythmia in
these patients (Aims 2 and 3)?
We will use iPSC-derived cardiomyocytes from dilated cardiomyopathy (DCM) patients (Project 1 and
CRISPR genome editing) as the first step to study mechanisms at the protein and signaling level and
to identify candidate drug targets. To date, physiological screening of cardiomyocytes has lacked the
throughput and prediction accuracy needed to systematically probe mechanisms and discover
therapeutic targets. Project 3 will use instrument and iPSC-cardiomyocyte technology we developed
over the last decade to overcome this limitation. The conclusions that will be drawn from iPSC-
cardiomyocytes about mechanisms and candidate drug targets will be evaluated in lower throughput
adult cardiomyocyte preparations (within Projects 1 and 2) and in multiscale computational modeling
(with Core B) to confirm and extend hypotheses, thereby generating new insight relevant to the intact
human heart.
Our team, within the Project and PPG, is highly synergistic and uniquely appropriate to carry out this
large-scale project that should yield translationally actionable insights to ultimately improve patient
management and create safer, more effective therapeutics.

## Key facts

- **NIH application ID:** 10249149
- **Project number:** 5P01HL141084-03
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** MARK MERCOLA
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $513,960
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10249149

## Citation

> US National Institutes of Health, RePORTER application 10249149, Project 3 (Mercola) (5P01HL141084-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10249149. Licensed CC0.

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